13, 14 Dehydro PGF3 compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin and analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 657,738, filed Feb. 13, 1976, now issued as U.S. Pat. No. 4,018,803, on Apr. 19, 1977.

The present invention relates to prostaglandin analogs for which the essential material constituting a disclosure therefor is incorporated by reference here from U.S. Pat. No. 4,018,803, issued April 19, 1977. 

I claim:
 1. A compound of the formula ##STR1## wherein Y₁ is --C.tbd.C--; wherein g is 1, 2, or 3;Wherein M₁ is ##STR2## wherein R₅ and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ is methyl only when the other is hydrogen; Wherein L₂ is ##STR3## or a mixture of ##STR4## wherein R₃ and R₄ are hydrogen or fluoro, being the same or different, with the proviso that at least one of R₃ and R₄ is fluoro; and Wherein R₁ is hydrogen, alkyl of 1 to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with 1, 2, or 3 chloro or alkyl of 1 to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 2. A compound according to claim 1, wherein g is
 3. 3. A compound according to claim 2, wherein R₃ and R₄ are both fluoro.
 4. A compound according to claim 3, wherein R₅ and R₆ are hydrogen.
 5. 2A,2B-Dihomo-16,16-difluoro-13,14-didehydro-PFG₃α, methyl ester, a compound according to claim
 4. 6. A compound according to claim 1, wherein g is
 1. 7. A compound according to claim 6, wherein both R₃ and R₄ are fluoro.
 8. A compound according to claim 7, wherein R₅ and R₆ are hydrogen.
 9. 16,16-Difluoro-13,14-didehydro-PGF₃α, methyl ester, a compound according to claim
 8. 10. A compound of the formula ##STR5## wherein Y₁ is --C.tbd.C--; wherein g is 1, 2, or 3;wherein M₂ is ##STR6## wherein L₃ is ##STR7## or a mixture of ##STR8## wherein R₃ and R₄ are hydrogen or methyl, being the same or different; and wherein R₁ is hydrogen, alkyl of 1 to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with 1, 2, or 3 chloro or alkyl of 1 to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 11. A compound according to claim 10, wherein g is
 1. 12. A compound according to claim 11 wherein at least one of R₃ and R₄ is methyl.
 13. A compound according to claim 12, wherein R₃ and R₄ are both methyl.
 14. A compound according to claim 11, wherein R₃ and R₄ are hydrogen.
 15. 13,14-Didehydro-PGF₃α, methyl ester, 15-methyl ether, a compound according to claim
 14. 16. A compound of the formula ##STR9## wherein Y₁ is --C.tbd.C--; wherein g is 1, 2, or 3;wherein M₃ is ##STR10## wherein R₅ is hydrogen or methyl; wherein L₄ is ##STR11## or a mixture of ##STR12## wherein R₂ and R₃ are hydrogen or methyl, being the same or different, with the proviso that one of R₃ and R₄ is methyl; and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 17. A compound according to claim 16, where g is
 3. 18. A compound according to claim 17, wherein R₃ and R₄ are both methyl.
 19. A compound according to claim 18, wherein R₅ is hydrogen.
 20. 2a,2b-Dihomo-16,16-dimethyl-13,14-didehydro-PGF₃α, methyl ester, a compound according to claim
 19. 21. A compound according to claim 16, wherein g is
 1. 22. A compound according to claim 21, wherein R₃ and R₄ are both methyl.
 23. A compound according to claim 22, wherein R₅ is hydrogen.
 24. 16,16-Dimethyl-13,14-didehydro-PGF₃α, methyl ester, a compound according to claim
 23. 25. A compound of the formula ##STR13## wherein Y₁ is --C.tbd.C--; wherein g is 1, 2, or 3;wherein M₁ is ##STR14## wherein R₅ and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ is methyl only when the other is hydrogen; wherein L₂ is ##STR15## or a mixture of ##STR16## wherein R₃ and R₄ are hydrogen or fluoro, being the same or different, with the proviso that at least one of R₃ and R₄ is fluoro; and wherein R₁ is hydrogen, alkyl of 1 to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with 1, 2, or 3 chloro or alkyl of 1 to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 26. A compound according to claim 25 wherein g is
 3. 27. A compound according to claim 26 wherein R₃ and R₄ are both fluoro.
 28. A compound according to claim 27 wherein R₅ and R₆ are hydrogen.
 29. 2a2b-Dihomo-16,16-difluoro-13,14-didehydro-8β, 12α-PGF₃α, methyl ester, a compound according to claim
 28. 30. A compound according to claim 29, wherein g is
 1. 31. A compound according to claim 30, wherein both R₃ and R₄ are fluoro.
 32. A compound according to claim 31, wherein R₅ R₆ are hydrogen.
 33. 16,16-Difluoro-13,14-didehydro-8β,12α-PGF₃α, methyl ester, a compound according to claim
 32. 34. A compound of the formula ##STR17## wherein Y₁ is --C.tbd.C--; wherein g is 1, 2, or 3;wherein M₂ is ##STR18## wherein L₃ is ##STR19## or a mixture of ##STR20## wherein R₃ and R₄ are hydrogen or methyl, being the same or different; and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 35. A compound according to claim 34, wherein g is
 1. 36. A compound according to claim 35, wherein at least one of R₃ and R₄ is methyl.
 37. A compound according to claim 36, wherein R₃ and R₄ are both methyl.
 38. A compound according to claim 35, wherein R₃ and R₄ are hydrogen.
 39. 13,14-Didehydro-8β,12α-PGF₃α, methyl ester, 15-methyl ether, a compound according to claim
 38. 40. A compound of the formula ##STR21## wherein Y₁ is --C.tbd.C--; wherein g is 1, 2, or 3;wherein M₃ is ##STR22## wherein R₅ is hydrogen or methyl; wherein L₄ is ##STR23## or a mixture of ##STR24## wherein R₃ and R₄ are hydrogen or methyl, being the same or different, with the proviso that one of R₃ and R₄ is methyl; and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 41. A compound according to claim 40, wherein g is
 3. 42. A compound according to claim 41, wherein R₃ and R₄ are both methyl.
 43. A compound according to claim 42, wherein R₅ is hydrogen.
 44. 2a,2b-Dihomo-16,16-dimethyl-13,14-didehydro-8β,12α-PGF₃α, methyl ester, a compound according to claim
 43. 45. A compound according to claim 40, wherein g is
 1. 46. A compound according to claim 45, wherein R₃ and R₄ are both methyl.
 47. A compound according to claim 46, wherein R₅ is hydrogen.
 48. 16,16-Dimethyl-13,14-didehydro-8β,12α-PGF₃α, methyl ester, a compound according to claim
 47. 